Immortalization of neuroendocrine pinealocytes from transgenic mice by targeted tumorigenesis using the tryptophan hydroxylase promoter

Tryptophan hydroxylase (TPH) is the first enzyme in both serotonin and melatonin biosynthesis in neuroendocrine cells of the pineal gland. The lack of immortalized neuroendocrine pineal cell lines has been a major obstacle to the study of the tissue-specific and circadian regulation of TPH gene expression in the pineal gland. Previously, we demonstrated that a 6.1 kb 5' upstream region of the mouse TPH gene directs the restricted expression of a lacZ reporter gene to the pineal gland and the raphe nuclei of transgenic mice. Therefore, to develop TPH-expressing pineal cell lines we first established transgenic mice carrying a construct consisting of 6.1 kb of 5' flanking region fused to the SV40 T-antigen. These animals developed highly invasive pineal tumors and died at 12-15 weeks of age. The pineal tumors obtained from the transgenic mice were utilized to establish the immortalized pinealocyte-derived cell lines. These cells express two marker enzymes, TPH and serotonin N-acetyltransferase (NAT). In pineal gland TPH and NAT expressions have been known to be regulated during circadian cycle. The two established cell lines therefore promise to be a valuable in vitro model system for the study of the rhythmic nature of the pineal function at molecular level in mammal.     

Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity

We here demonstrated the prophylactic effect of an extract (KM-110) from Viscum album coloratum, a Korean mistletoe, on tumor metastasis produced by highly metastatic tumor cells, colon 26-M3.1 carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental models in mice. Intravenous (i.v.) administration of KM-110 (100 microg/mouse) 2 days before tumor inoculation significantly inhibited lung metastasis of B16-BL6 and colon 26-M3.1 cells, and liver and spleen metastasis of L5178Y-ML25 cells. The prophylactic effect of KM-110 on tumor metastasis was evident with various administration routes, i.e. subcutaneous, oral, intranasal as well as i.v., and was dependent upon the dose of KM-110 administered. Furthermore, mice given KM-110 (100 microg) 2 days before tumor inoculation showed significantly prolonged survival rates compared with the untreated mice. In a time course analysis of NK activity, i.v. administration of KM-110 (100 microg) significantly augmented NK cytotoxicity to Yac-a tumor cells from 1 to 3 days after KM-110 treatment. Furthermore, depletion NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of KM-110 on lung metastasis of colon 26-M3.1 cells. These results suggest that KM-110 possesses immunopotentiating activity which enhances the host defense system against tumors, and that its prophylactic effect on tumor metastasis is mediated by NK cell activation.     

The effects of covering on complex wave propagation in gyromagneticslotlines

The evolution of complex leaky waves in partially open gyromagnetic slotlines into complex modes in a shielded slotline is presented. Given a particular stratified gyromagnetic slotline with two sidewalls present, four types (Types I-IV) of guided structures are defined and investigated, depending upon the four possible combinations of top and bottom covers. The behavior of the complex solutions is discussed for the partially open gyromagnetic slotlines. Initially, the slotline of Type I, which lacks both top and bottom covers, shows that no coupling exists among various pairs of leaky waves. By adding only a top cover into Type I, the resultant slotline of Type II exhibits certain coupling between different sets of leaky waves. Similarly, by adding only a bottom cover into Type I, the resultant slotline of Type III shows that certain strong leaky waves of Types I and II now become weak leaky waves. From these numerical experiments, we deduce that the complex modes supported by Type IV, which is completely shielded, can be the result of the mode coupling of the two previously found leaky waves in Types II and III waveguides, respectively. Therefore, the formation of complex modes in shielded slotline is related to the effects of covering on mode coupling of the various leaky waves of the partially open slotlines     

Synthesis and biological properties of new 1 beta-methylcarbapenems

The synthesis and biological activity of the novel series of 1 beta-methylcarbapenems, 1 and 2 were described. Most compounds displayed high potent antibacterial activity. The best compound in this series, 2a (IH201; R2 = NH2) showed an excellent and a broad spectrum as well as high renal DHP-I stability. It also possessed good in vivo efficacy and high safety.     

Protective Effect of Microencapsulation Consisting of Multiple Emulsification and Heat Gelation Processes on Immunoglobulin in Yolk

ABSTRACT: Two different emulsification methods involving multiple emulsification and heat gelation were used for preparation of whey protein-based microcapsules containing immunoglobulin in yolk (IgY). The residual activity of IgY during the emulsion preparation and the effects of microencapsulation on IgY stability under harsh conditions were investigated. The residual activity of IgY in an emulsion prepared with a membrane emulsifier was higher than for an emulsion using a homogenizer. Microencapsulated IgY showed remarkable stability against both pepsin and acid. Both microencapsulated IgY and nonencapsulated IgY were relatively stable in bile and artificial intestinal juice. Microencapsulated IgY retained 74% of initial activity during heat treatment. There were no significant differences in the residual activities of microencapsulated IgY under storage temperatures of 4, 25, and 37°C.     

Time-domain seismic reliability of nonlinear structures

A novel reliability analysis technique is presented to estimate the reliability of real structural systems. Its unique feature is that the dynamic loadings can be applied in time domain. It is a nonlinear stochastic finite element logarithm combined with the response surface method (RSM). It generates the response surface around the most probable failure point and incorporates information of the distribution of the random variables in the RSM formulation. It is verified using the Monte Carlo simulation technique, and is found to be very efficient and accurate. Most sources of nonlinearlity and uncertainty can be explicitly incorporated in the formulation. The flexibility of connections, represented by moment-relative rotation(M-θ) curves, is addressed. After the Northridge earthquake of 1994, several improved steel connections were proposed. Structural Sesimic Design Associates (SSDA) tested several full-scale proprietory slotted web beam-column connections. The authors suggested(M-θ) curves for this connection using actual test data. Behaviours of steel frames, assuming the connections are fully restrained, partially restrained, consisting of pre and post-Northridge connections are evaluated and compared. Desirable features of the post-Northridge connections observed during testing are analytically confirmed. Laterally weak steel frame is then strengthened with concrete shear walls. Capabilities and the advanced nature of the method are demonstrated with the help of realistic examples. This paper is dedicated to Prof R N Iyengar of the Indian Institute of Science on the occasion of his formal retirement.     

Molecular and biologic characterization of a newly established Philadelphia-positive acute lymphoblastic leukemia cell line (Z-33) with an autocrine response to GM-CSF

We have recently established a new Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) cell line, designated Z-33. This line has L2 morphology, ultrastructural characteristics of lymphoblasts and typical B lineage surface markers identical to those observed in the Ph1-positive ALL patient from whom the line was derived. In addition, a rearranged immunoglobulin heavy-chain gene (JH) band was found in Z-33 cells by Southern blot analysis, confirming B cell clonality. Cytogenetic analysis of the cell line revealed t(9;22)(q34;q11.2). Polymerase chain reaction (PCR)-amplified cDNA from Z-33 cells demonstrated an e1-az BCR-ABL junction, and the p190BCR-ABL protein was detected in them by the immune complex kinase assay. Z-33 cells produce interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta, Neither IL-1 beta, G-CSF, TNF-alpha, nor their corresponding antibodies affected the cell line's growth. In contrast, anti-GM-CSF neutralizing antibodies suppressed Z-33 colony formation, and GM-CSF stimulated it in a dose-dependent fashion. In addition, receptor studies with biotinylated GM-CSF demonstrated specific binding to Z-33 cells, indicating that the cells express GM-CSF receptors. Taken together, our data suggest that the Ph1-positive Z-33 ALL cells produce GM-CSF, express GM-CSF receptors, and show an autocrine proliferative response to this cytokine.     

Locally recurrent carcinoma of the breast. Results of radiation therapy

Local and regional recurrences are frequent problems in breast cancer management. Radiation therapy is effective in producing long term remission. This study evaluates the results of radiation therapy of 215 patients with recurrent disease limited to the chest wall and/or regional lymph node areas. The local results showed complete control in 67% of cases (mean and median durations 32 months and 22 months, respectively), partial control in 24% of cases (mean and median 11 and 8 months, respectively) and no control in the remaining 9%. The radiation dose recommended for the treatment of recurrent mammary carcinoma is 5000 rads in 5 weeks for relatively small lesions. Supplementary local doses of 500-1000 rads in 1 week may be given to bulky lesions as necessary for residual disease. Although local relapse indicates a poor prognosis, it is by no means totally hopeless. Of 215 patients treated 44 (21%) survived 5 years and 10 (5%) survived 10 years following radiation therapy of recurrent disease. There were seven patients, or 3%, who were free of cancer at 5 to 15 years. Radiation therapy was valuable in controlling local lesions, and thus, in improving quality of survival, even in those patients who eventually died of metastatic disease.     

Acute effects of chundosunbup qi-training on blood concentrations of TSH, calcitonin, PTH and thyroid hormones in elderly subjects

The present study investigated how the systemic treatment of a programmed exercise, ChunDoSunBup (CDSB) Qi-training, affects the secretion of thyroid and parathyroid hormones in elderly subjects (10 male and 5 female). Plasma concentrations of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), parathyroid hormone (PTH), ionized calcium, and calcitonin were determined. CDSB Qi-training induces a slight increase in TSH. Both T4 and T3 were increased at the mid-time of CDSB Qi-training (p < 0.05). There were significant correlations only between T3 and T4 at mid-training. This shows that increase in the plasma level of T3 was associated with the secretion of T4. The plasma concentrations of calcitonin and PTH were increased at mid-time and post-time of CDSB Qi-training. But ionized calcium was decreased slightly by CDSB Qi-training. These results suggest that Qi-training modulates the secretion of thyroid hormones, calcium metabolism, and parathyroid hormones in the elderly. However, whether the long-term practice of CDSB Qi-training might change bone metabolism and have longitudinal effects on the thyroid hormone of the elderly need further investigation.     

Expression of vimentin and cytokeratin in eutopic and ectopic endometrium of women with adenomyosis and ovarian endometrioma

Tuberculosis is a continuous threat for health in all parts of the world. In industrialized centers an emerging increase of tuberculosis is observed due to low health standards, poor health education and control, increasing migration and the HIV epidemic. This should alert the pediatrician, since most tuberculosis infections in childhood start with contacts of infected adults with children. There is still a good response to most drugs against tuberculosis, but in some parts of the world the resistance to conventional treatment is an emerging problem. In general incidence, morbidity and mortality of tbc in children of the western world is low and has good prognosis. However, the diagnostic principles and the education of pediatricians for recognizing tbc is still of utmost importance.